Expert Opinion on Therapeutic Targets最新文献_第2页

Senolytics for cancer treatment: complexities and opportunities. 癌症治疗的老年学：复杂性和机遇。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-27 DOI: 10.1080/14728222.2026.2738910

Sofian Al Shboul, David A Gewirtz, Tareq Saleh

{"title":"Senolytics for cancer treatment: complexities and opportunities.","authors":"Sofian Al Shboul, David A Gewirtz, Tareq Saleh","doi":"10.1080/14728222.2026.2738910","DOIUrl":"10.1080/14728222.2026.2738910","url":null,"abstract":"Introduction: There is currently growing interest in targeting senescent tumor cells as a strategy for improving the efficacy of cancer therapy. Despite the promise of this strategy, a number of limitations have emerged relating to the utility of senescence-eliminating agents, collectively termed senolytics. First, these compounds show different outcomes in aging and tumor cell models. Second, they exhibit variable efficacy in eliminating senescent tumor cells based on tumor background. Third, efficacious agents do not necessarily eliminate the risk of proliferative recovery that could reflect disease recurrence. Fourth, several of the compounds that demonstrate the highest efficacy against senescent tumor cells are associated with established or potential adverse effects that would limit their translation.Areas covered: Here, we provide an overview of the advantages and disadvantages of established senolytics and explore the potential for newly identified agents strictly tested in tumor cell models.Expert opinion: Senolytic translation is constrained by Therapy-induced Senescence (TIS) heterogeneity generating resistant subpopulations, potential proliferative recovery, senolytic-associated adverse effects, risk for targeting beneficial senescent cells, and absence of validated clinical trial designs. Emerging immune-based strategies nanovaccines, nano-antigen-presenting machinery, and CAR-T platforms offer more selective alternatives, but require validated preclinical and clinical testing for further implementation.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-16"},"PeriodicalIF":5.1,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular insights into GLP-1 receptor agonists and emerging metabolic-inflammatory targets in hidradenitis suppurativa. GLP-1受体激动剂和化脓性汗腺炎中新出现的代谢炎症靶点的分子见解。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-24 DOI: 10.1080/14728222.2026.2738341

Emma Brogaard, Valdemar Wendelboe Nielsen, Nadja Højgaard Pedersen, Simon Francis Thomsen

{"title":"Molecular insights into GLP-1 receptor agonists and emerging metabolic-inflammatory targets in hidradenitis suppurativa.","authors":"Emma Brogaard, Valdemar Wendelboe Nielsen, Nadja Højgaard Pedersen, Simon Francis Thomsen","doi":"10.1080/14728222.2026.2738341","DOIUrl":"10.1080/14728222.2026.2738341","url":null,"abstract":"Introduction: Hidradenitis suppurativa (HS) is increasingly recognized as a systemic immunometabolic disease associated with obesity, insulin resistance, and metabolic syndrome (MetS). A metabolically unhealthy lean phenotype indicates that metabolic dysfunction and chronic low-grade inflammation may occur independently of increased body mass index (BMI) in patients with HS. Reduced effectiveness of biologic therapies in patients with obesity further supports targeting the upstream metabolic drivers of inflammation.Areas covered: This review outlines metabolic-inflammatory pathways proposed to contribute to HS, including insulin/insulin-like growth factor 1 (IGF-1) signaling, mechanistic target of rapamycin complex 1 (mTORC1) overactivation, adipokine dysregulation, and gut-skin interactions. Building on this framework, this review evaluates evidence on glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual incretin agonists, and other metabolic interventions, including metformin is evaluated.Expert opinion: GLP-1RAs may serve as adjunctive metabolic therapies for selected patients with HS and obesity or MetS. By promoting weight loss and metabolic improvement, they may reduce systemic inflammation, perioperative risk, and improve responses to weight-based biologics. However, current evidence remains mainly observational and is confounded by concomitant therapies. Randomized controlled trials using well-defined dermatological and metabolic endpoints are needed before routine implementation.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-15"},"PeriodicalIF":5.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In the wisdom of Odin: modular architecture, receptor trafficking and therapeutic implications. 奥丁的智慧：模块化建筑，受体运输和治疗意义。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-22 DOI: 10.1080/14728222.2026.2738190

Valeria Pennacchietti, Francesca Malagrinò, Stefano Gianni

{"title":"In the wisdom of Odin: modular architecture, receptor trafficking and therapeutic implications.","authors":"Valeria Pennacchietti, Francesca Malagrinò, Stefano Gianni","doi":"10.1080/14728222.2026.2738190","DOIUrl":"10.1080/14728222.2026.2738190","url":null,"abstract":"Introduction: Odin (ANKS1A) is a multidomain adaptor protein originally identified as a substrate of receptor tyrosine kinases. Over the past two decades, studies have revealed functions that extend beyond canonical growth factor signaling. At the molecular level, Odin participates in receptor signaling and membrane trafficking pathways, while at the cellular and physiological levels it contributes to processes such as ependymal cell development, ciliogenesis, and neurovascular homeostasis. Consistent with these diverse functions, alterations in Odin expression or activity have been linked to an expanding spectrum of human diseases, including cancer, neurodevelopmental disorders, neurodegeneration, ciliopathies, and cardiovascular diseases.Areas covered: In this review, we summarize current knowledge of Odin structure and function, with particular emphasis on how its conserved modular architecture may support its role as a coordinator of receptor trafficking, signaling, and membrane homeostasis. We further discuss emerging evidence linking Odin dysfunction to human diseases and review the limited therapeutic strategies currently available.Expert opinion: Collectively, we propose a model in which Odin functions through its conserved multidomain architecture. A deeper understanding of its structural organization and molecular mechanisms may not only reveal fundamental principles of receptor regulation but also establish Odin as a promising, yet largely unexplored, therapeutic target.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-13"},"PeriodicalIF":5.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploiting ER proteostasis in malaria: protein disulphide isomerases as selective antimalarial targets. 利用内质网蛋白酶在疟疾：蛋白二硫异构酶作为选择性抗疟疾靶点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-01 Epub Date: 2026-09-06 DOI: 10.1080/14728222.2026.2723486

Adeshina I Odugbemi, Wendy Mthembu, Tawanda Zininga

{"title":"Exploiting ER proteostasis in malaria: protein disulphide isomerases as selective antimalarial targets.","authors":"Adeshina I Odugbemi, Wendy Mthembu, Tawanda Zininga","doi":"10.1080/14728222.2026.2723486","DOIUrl":"10.1080/14728222.2026.2723486","url":null,"abstract":"Introduction: The emergence of partial resistance to artemisinin-based therapies has intensified the search for antimalarial targets beyond classical kinases and proteases. Protein disulfide isomerases (PDIs) have emerged as attractive candidates due to their roles in endoplasmic reticulum (ER) oxidative folding, redox homeostasis, and survival under proteotoxic stress. Several Plasmodium falciparum PDI family members are essential during asexual blood stages and contribute to parasite transmission.Areas covered: We summarize PfPDI architecture, catalytic and holdase functions, and their integration within the parasite ER folding network, highlighting structural divergence from human PDIs that may enable selective inhibition. We review PDI-directed chemotypes, including covalent active-site binders and non-covalent/allosteric modulators, and highlight the absence of PfPDI-selective probes with validated intracellular mechanisms. We further discuss approaches for target validation, including chemoproteomics, activity-based profiling, and chemical genetics, alongside medicinal chemistry considerations for achieving exposure to an intracellular ER target. Finally, we examine PfPDIs within a proteostasis-stress framework and discuss combination strategies with protein-damaging agents such as artemisinin derivatives.Expert opinion: Progress will depend on structure-guided targeting of divergent non-catalytic surfaces, optimization of intracellular and ER exposure, and rigorous in-parasite target-engagement studies. PfPDI inhibitors are most likely to succeed as components of resistance-robust combination therapies.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1015-1035"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing the glymphatic system as a potential pathway to limit Parkinson disease progression. 增强淋巴系统作为限制帕金森病进展的潜在途径。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-01 Epub Date: 2026-09-24 DOI: 10.1080/14728222.2026.2738182

Zhao Yan, Jason Howitt

引用次数: 0

Targeting the NLRP3 inflammasome pathway associated with neuroinflammation mediated Alzheimer's disease: pre-clinical and clinical status of emerging therapeutics. 靶向与神经炎症介导的阿尔茨海默病相关的NLRP3炎性体途径：新兴治疗方法的临床前和临床状况

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-01 Epub Date: 2026-08-27 DOI: 10.1080/14728222.2026.2723488

Devesh Yaduvanshi, Rishabh Aggarwal, Sameeya A, Mohd Aqil, Mohd Mujeeb, Mohd Akhtar, Abul Kalam Najmi

{"title":"Targeting the NLRP3 inflammasome pathway associated with neuroinflammation mediated Alzheimer's disease: pre-clinical and clinical status of emerging therapeutics.","authors":"Devesh Yaduvanshi, Rishabh Aggarwal, Sameeya A, Mohd Aqil, Mohd Mujeeb, Mohd Akhtar, Abul Kalam Najmi","doi":"10.1080/14728222.2026.2723488","DOIUrl":"10.1080/14728222.2026.2723488","url":null,"abstract":"Introducion: Alzheimer's disease (AD) is a rising global health problem, but current treatments only target symptoms rather than fixing their underlying root causes. A major pathological feature is neuroinflammation, which is specifically driven by the Nucleotide-binding domain, Leucine-rich-repeat and Pyrin domain-containing 3 (NLRP3) inflammasome cascade, which acts as a 'molecular switch' that causes immune cells in the brain to trigger robust secretion of pro-inflammatory cytokines (e.g. IL-1β, IL-18) and pyroptosis, causing systemic inflammation, consequently, neuroinflammation.Areas covered: This review breaks down the pathways triggered by immune cells activation (neurotoxic microglial phenotype) and mainly focuses on the NLRP3 inflammasome neuroinflammation pathway. It explores the promising therapeutic potential of specific bioactive phytochemicals, repurposed and novel synthetic drugs/agents, to shut-down this molecular switch, i.e. NLRP3 inflammasome pathway.Expert opinion: To truly stop AD, we must shift our focus from treating merely the symptoms, by stopping the disease at its roots. While discovering the novel NLRP3 inflammasome inhibitors is exciting, the biggest hurdle is getting them into the brain. The future of AD treatment relies on combining these targeted drugs with advanced nanotechnology, like nano-particles, to successfully cross the blood-brain barrier (BBB) and safely deliver the drugs exactly where they are needed.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"995-1014"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the Orai1 CRAC channel: translating molecular insights into therapeutic progress. 靶向Orai1 CRAC通道：将分子见解转化为治疗进展

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-01 Epub Date: 2026-09-23 DOI: 10.1080/14728222.2026.2738180

Isaac Jardín, Alvaro Macias-Díaz, Vanesa Jimenez-Velarde, Manuel Fuentes-Mateos, Tarik Smani, Juan A Rosado

{"title":"Targeting the Orai1 CRAC channel: translating molecular insights into therapeutic progress.","authors":"Isaac Jardín, Alvaro Macias-Díaz, Vanesa Jimenez-Velarde, Manuel Fuentes-Mateos, Tarik Smani, Juan A Rosado","doi":"10.1080/14728222.2026.2738180","DOIUrl":"10.1080/14728222.2026.2738180","url":null,"abstract":"Introduction: The Ca2+ release-activated Ca2+ (CRAC) channel, triggered by the interaction between the Ca2+ sensor STIM1 and Orai1, is the primary mediator of store-operated calcium entry (SOCE). Dysregulation of this process drives numerous human pathologies, particularly immune disorders and cancer hallmarks. Due to its role, Orai1 has emerged as an attractive target for precision therapeutics.Areas covered: This review outlines the pharmacological evolution of CRAC channel modulators, tracing their development from early chemical tools, such as SKF-96365, that exhibits several off-target effects, to more selective second-generation pore blockers, including Synta66, RO2959 or GSK-7975A. Particular attention is paid to third-generation inhibitors, especially CM4620 (zegocractin), evaluating data from recent Phase 2 clinical trials in acute pancreatitis (CARPO), severe COVID-19 pneumonia (CARDEA), and acute kidney injury (KOURAGE). We describe emerging orally bioavailable candidates like CM5480 aimed at chronic cardiopulmonary remodeling.Expert opinion: Clinical experience reveals that targeting ubiquitous Ca2+ pathways, such as SOCE, demands specific trial design, transitioning toward biomarker-driven stratification of patient cohorts. Over the coming years, the pharmacological design will diverge into acute intravenous critical care and chronic oral immunomodulation. Ultimately, the exploitation of tissue-specific Orai2 and Orai3 isoform profiles represents the next frontier to enhance therapeutic efficacy across distinct disorders.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"955-970"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sirtuin signaling as therapeutic targets of immunosenescence. Sirtuin信号作为免疫衰老的治疗靶点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1080/14728222.2026.2737637

Anna Calabrò, Giulia Accardi, Anna Aiello, Calogero Caruso, Damiano Galimberti, Chiara Puleo, Rosa Zarcone, Giuseppina Candore

{"title":"Sirtuin signaling as therapeutic targets of immunosenescence.","authors":"Anna Calabrò, Giulia Accardi, Anna Aiello, Calogero Caruso, Damiano Galimberti, Chiara Puleo, Rosa Zarcone, Giuseppina Candore","doi":"10.1080/14728222.2026.2737637","DOIUrl":"10.1080/14728222.2026.2737637","url":null,"abstract":"Introduction: Aging is characterized by immunosenescence, encompassing, immune aging and inflammaging. Because immune competence is a critical determinant of lifespan and healthspan, targeting immunosenescence has become a major objective of geroscience. In this context, sirtuins have emerged as compelling therapeutic candidates.Areas covered: This review examines the role of sirtuin signaling in immunosenescence, focusing on its links with nicotinamide adenine dinucleotide (NAD)+ metabolism, oxidative stress, and inflammatory pathways. Pharmacological strategies aimed at enhancing sirtuin activity, including natural and synthetic activators as well as NAD+ precursors, are critically discussed.Expert opinion: Sirtuin signaling represents a biologically plausible strategy for targeting immunosenescence, as it integrates metabolic, mitochondrial, epigenetic, and inflammatory pathways involved in the age-related remodeling of innate and adaptive immunity. However, sirtuin modulation remains investigational rather than an established therapeutic approach. Although NAD+ precursors and sirtuin activators have yielded encouraging preclinical findings, robust evidence of clinically meaningful effects in humans is still lacking. Further progress will require validated biomarkers of immunosenescence, appropriately selected study populations, adequately powered randomized trials incorporating functional and clinically relevant immune endpoints, and long-term safety assessment. At present, mTOR-directed interventions appear closer to clinical translation, whereas NAD+- and sirtuin-based approaches remain promising complementary strategies requiring further investigation.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"971-993"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular targeting of CDK9 in oncology therapeutics: avenues for translational impact. CDK9在肿瘤治疗中的分子靶向：转化影响的途径。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-01 Epub Date: 2026-08-25 DOI: 10.1080/14728222.2026.2723483

Tiyao Liu, Zhongran Liu, Wenjing Wei, Shudong Wang, Shaoqiang Wang, Yuanyuan Zhang, Ziyi Gao, Wenhao Wu

{"title":"Molecular targeting of CDK9 in oncology therapeutics: avenues for translational impact.","authors":"Tiyao Liu, Zhongran Liu, Wenjing Wei, Shudong Wang, Shaoqiang Wang, Yuanyuan Zhang, Ziyi Gao, Wenhao Wu","doi":"10.1080/14728222.2026.2723483","DOIUrl":"10.1080/14728222.2026.2723483","url":null,"abstract":"Background: Cyclin-dependent kinase 9 (CDK9) is a central regulator of RNA polymerase II elongation and has emerged as a therapeutic target in tumors characterized by transcriptional addiction. Growing interest in selective inhibitors and targeted degraders has renewed attention to the translational potential of CDK9-directed therapy.Areas covered: This review summarizes the molecular functions of the CDK9/positive transcription elongation factor b (P-TEFb) axis, its role in super-enhancer-driven oncogenic programs, and the mechanisms by which CDK9 inhibition promotes apoptosis, epigenetic derepression, and tumor microenvironment remodeling. We also discuss representative small-molecule inhibitors and proteolysis-targeting chimera (PROTAC) degraders, emerging biomarkers for patient stratification, rational combination strategies, and the current landscape of resistance mechanisms.Expert opinion: Selective targeting of CDK9 offers a promising route for treating refractory malignancies, particularly when guided by transcriptional dependency, biomarker-informed dosing, and rational combination design. Future progress will likely depend on improving therapeutic index, refining translational biomarkers, and anticipating adaptive resistance during clinical development.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"929-940"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular targets in proliferative vitreoretinopathy: rethinking prevention, treatment and drug delivery after rhegmatogenous retinal detachment. 增殖性玻璃体视网膜病变的分子靶点：对孔源性视网膜脱离后的预防、治疗和给药的重新思考。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-01 Epub Date: 2026-09-08 DOI: 10.1080/14728222.2026.2724125

Enrico Bernardi, William Mitchell, Carla Troyas, Rodrigo Anguita

{"title":"Molecular targets in proliferative vitreoretinopathy: rethinking prevention, treatment and drug delivery after rhegmatogenous retinal detachment.","authors":"Enrico Bernardi, William Mitchell, Carla Troyas, Rodrigo Anguita","doi":"10.1080/14728222.2026.2724125","DOIUrl":"10.1080/14728222.2026.2724125","url":null,"abstract":"Introduction: Proliferative vitreoretinopathy (PVR) is the leading cause of surgical failure after rhegmatogenous retinal detachment repair and the principal indication for repeat vitreoretinal surgery, yet four decades of mechanistic research have not produced an effective pharmacological adjunct. This review reexamines why, and asks how prevention, treatment and drug delivery might be reframed.Areas covered: This narrative expert review conceptualizes PVR as a temporally evolving, overlapping fibro-inflammatory continuum spanning inflammation and chemotaxis, retinal pigment epithelial activation and epithelial-mesenchymal transition, proliferation, extracellular matrix deposition, membrane contraction and neurodegeneration. Informed by the current literature and the authors' experience, we appraise the key cellular drivers, the agents tested or proposed (corticosteroids, antimetabolites, anti-VEGF, anti-fibrotics and RNA-based approaches), emerging biology (mechanobiology, senescence, exosomes, epigenetics and ferroptosis), and the pharmacokinetic barriers and delivery platforms that constrain translation in the vitrectomized and oil-filled eye.Expert opinion: Repeated trial failure reflects not a single failed target but recurring problems of patient selection, disease timing, pharmacokinetic mismatch, biological redundancy and trial design. Progress will require biomarker-enriched prevention in high-risk eyes, stage-matched combination therapy, delivery systems suited to the vitrectomized eye, and adequately powered multicenter trials pairing high-quality surgery with appropriately timed pharmacology.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"941-954"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0